[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"detail-sidebar-cat-0-en-105":3,"doc-seo-352263-105":59,"doc-detail-352263-en":130},{"code":4,"msg":5,"data":6},0,"success",[7,13,18,23,28,33,38,43,48,51,55],{"id":8,"doc_module":4,"doc_module_name":9,"category_name":10,"show_sort_weight":11,"slug":12},1,"Document","Story & Novel",90,"story-novel",{"id":14,"doc_module":4,"doc_module_name":9,"category_name":15,"show_sort_weight":16,"slug":17},2,"Literature",80,"literature",{"id":19,"doc_module":4,"doc_module_name":9,"category_name":20,"show_sort_weight":21,"slug":22},4,"Exam",70,"exam",{"id":24,"doc_module":4,"doc_module_name":9,"category_name":25,"show_sort_weight":26,"slug":27},5,"Comic",60,"comic",{"id":29,"doc_module":4,"doc_module_name":9,"category_name":30,"show_sort_weight":31,"slug":32},6,"Technology",50,"technology",{"id":34,"doc_module":4,"doc_module_name":9,"category_name":35,"show_sort_weight":36,"slug":37},7,"Healthcare",40,"healthcare",{"id":39,"doc_module":4,"doc_module_name":9,"category_name":40,"show_sort_weight":41,"slug":42},8,"Research & Report",30,"research-report",{"id":44,"doc_module":4,"doc_module_name":9,"category_name":45,"show_sort_weight":46,"slug":47},9,"Religion & Spirituality",20,"religion-spirituality",{"id":46,"doc_module":4,"doc_module_name":9,"category_name":49,"show_sort_weight":46,"slug":50},"World Cup","world-cup",{"id":52,"doc_module":4,"doc_module_name":9,"category_name":53,"show_sort_weight":52,"slug":54},10,"Lifestyle","lifestyle",{"id":56,"doc_module":4,"doc_module_name":9,"category_name":57,"show_sort_weight":24,"slug":58},19,"General","general",{"code":4,"msg":60,"data":61},"ok",{"site_id":62,"language":63,"slug":64,"title":65,"keywords":66,"description":67,"schema_data":68,"social_meta":123,"head_meta":125,"extra_data":127,"updated_unix":129},105,"en","pp2a-activation-targets-mycn-in-neuroblastoma","PP2A activation targets MYCN in neuroblastoma","","Neuroblastoma (NBL) is the most common extracranial childhood solid tumor, and high-risk cases often lack therapies that deliver durable benefit. MYCN amplification is a key determinant of high-risk disease, yet direct MYCN targeting has not succeeded. The study tests whether MYCN could be a functional target of PP2A and whether reactivating PP2A suppresses NBL. Pharmacologic PP2A activators ATUX-1215 and ATUX-5800 reduced MYCN mRNA, phosphorylation, and protein levels, linked to changes in H3K27ac and transcriptional regulators, and decreased tumor growth in vivo.",{"@graph":69,"@context":122},[70,84,105],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":35,"@type":76,"position":81},"https://docshare.wps.com/document/healthcare/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/pp2a-activation-targets-mycn-in-neuroblastoma/352263/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":99,"encodingFormat":97,"isAccessibleForFree":100,"interactionStatistic":101},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/pp2a-activation-targets-mycn-in-neuroblastoma/352263.png","ImageObject",300,407,{"name":92,"@type":93},"Patrick","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-24","2026-09-22",true,{"@type":102,"interactionType":103,"userInteractionCount":39},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"Why is MYCN considered central in high-risk neuroblastoma?","Question",{"text":112,"@type":113},"MYCN amplification is a well-established major factor for high-risk classification, driving aggressive development and poor prognosis through multiple aberrant mechanisms. Despite its importance, direct MYCN targeting has been ineffective.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"What hypothesis guides the study on PP2A and MYCN?",{"text":117,"@type":113},"The authors hypothesize that MYCN may be a target of PP2A and that reactivating PP2A could exert tumor-suppressive effects in neuroblastoma. They focus on phenotypic, epigenetic, and in vivo consequences of pharmacologic PP2A activation.",{"name":119,"@type":110,"acceptedAnswer":120},"How do ATUX-1215 and ATUX-5800 affect MYCN and tumor growth?",{"text":121,"@type":113},"ATUX-1215 and ATUX-5800 reduce MYCN mRNA abundance, phosphorylation, and protein expression. PP2A activation also decreases H3K27ac at the MYCN promoter and leads to reduced tumor growth in animals, with decreased MYCN expression confirmed in tumor specimens.","https://schema.org",{"og:url":83,"og:type":124,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":126,"canonical":83},"index,follow",{"doc_id":128,"site_id":62},352263,1790195167,{"code":4,"msg":5,"data":131},{"doc_id":128,"user_id":132,"nickname":92,"user_avatar":133,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":67,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":39,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":139,"language":140,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":141,"faqs":142,"seo_title":143,"seo_description":67,"update_tm":144,"read_time":145},549758146520,"https://ap-avatar.wpscdn.com/avatar/80002397d8c0411e94?_k=1775819394049821470","[www.nature.com/cddis](www.nature.com/cddis)  \nARTICLE OPEN   \nPP2A activation targets MYCN in neuroblastoma  \nNazia Nazam 1, Shamza Manzoor2, Maryam Shaikh1, Morgan L. Brown1, Janet R. Julson 1, Colin H. Quinn 1, Swatika Butey1, Sorina N. Shirley 1, Jamie M. Aye3, Karina Yoon4, Jianmei W. Leavenworth2, Michael Ohlmeyer5 and Elizabeth A. Beierle 1 ✉  \n© The Author(s) 2025  \n\n| | Neuroblastoma (NBL) is the most common extracranial solid tumor of childhood, accounting for 7-10% of all children cancers, but leading to 15% of childhood cancer related deaths. Children with high-risk neuroblastoma (HR-NBL) lack effective treatments that achieve durable outcomes. While multiple factors stratify NBL patients into the high- risk category, MYCN amplification is a crucial determinant for that group. Thus far, efforts towards directly targeting MYCN have proven unsuccessful. Serine/threonine protein phosphatase 2 A (PP2A) functions as a tumor suppressor across cancers through its epigenetic effects, and its activity and tumor suppressor function are inhibited in NBL. We hypothesized that MYCN may be a target for PP2A, and that reactivation of PP2A may have a tumor suppressive effect on NBL. We employed studies to document the phenotypic, epigenetic, and in vivo effects of pharmacologic PP2A activation. Novel PP2A activators, ATUX-1215 or ATUX-5800, reduced MYCN mRNA abundance and MYCN phosphorylation and protein expression. PP2A activation decreased the acetylation of H3K27 (H3K27ac) as well as the enrichment of H3K27ac at the MYCN promoter. ATUX-1215 and ATUX-5800 treatment led to hypophosphorylation of RNA Pol II carboxyterminal domain (CTD) and BRD4, transcriptional and epigenetic regulators respectively, coinciding with decreased MYCN expression and gene regulator acetylation. Tumor growth decreased in animals treated with ATUX-1215, and analysis of tumor specimens confirmed decreased MYCN expression. We conclude that pharmacologic PP2A reactivation may be a relevant | |\n| --- | --- | --- |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n|  |  | |\n|  |  |  |\n| | therapeutic component in NBL treatment through its targeting of MYCN. | |\n|  | Cell Death and Disease (2026)17:42; [https://doi.org/10.1038/s41419-025-08253-0](https://doi.org/10.1038/s41419-025-08253-0) |  |\n|  |  |  |\n\nINTRODUCTION  \nNeuroblastoma (NBL) is derived from precursor or immature cells of the sympathetic nervous system and is one of the most diffuse and highly malignant childhood cancers. As of 2021, an estimated 10,500 children in the US were diagnosed annually with cancer, of which 6% were NBL [1] . Significant advances have been made towards improving outcomes for patients with NBL, yet high-risk NBL (HR-NBL) continues to show an aggressive development pattern and dismal prognosis with a 5-year survival not surpassing 50%, compared to low and intermediate-risk patients in whom survival reaches 85-90% . This sub-set of NBL patients have limited availability of new therapeutic options and practically none that result in long-term survival, providing a stimulus to develop novel therapeutics to improve patient outcomes.  \nWhile multiple features stratify NBL patients into the high-risk category, MYCN amplification in the tumor is well established asthe major factor leading to classification of a patient as having high-risk disease [2–4] . Aberrant MYCN levels due to enhanced transcription, protein stability, gene amplification and posttranslational modifications (PTMs) confer MYCN pathogenicity [3, 5] . As an example, this single gene amplification is sufficient as anoncogenic driver to induce neoplastic transformation in neural crest- derived cells [4] . In this context, MYCN represents an ideal  \ntherapeutic target given its correlation with rapid tumor progression, poor prognosis and the limited expression in normal cells and tissue, suggesting high tolerability for a MYCN-targeted approach [3, 6] .","cbCaij4exRTbfDx6","https://ap.wps.com/l/cbCaij4exRTbfDx6","pdf",3996164,11,"English","# Introduction\n## Neuroblastoma background and high-risk features\n## MYCN amplification as a therapeutic target\n## Rationale for PP2A activation","[{\"question\":\"Why is MYCN considered central in high-risk neuroblastoma?\",\"answer\":\"MYCN amplification is a well-established major factor for high-risk classification, driving aggressive development and poor prognosis through multiple aberrant mechanisms. Despite its importance, direct MYCN targeting has been ineffective.\"},{\"question\":\"What hypothesis guides the study on PP2A and MYCN?\",\"answer\":\"The authors hypothesize that MYCN may be a target of PP2A and that reactivating PP2A could exert tumor-suppressive effects in neuroblastoma. They focus on phenotypic, epigenetic, and in vivo consequences of pharmacologic PP2A activation.\"},{\"question\":\"How do ATUX-1215 and ATUX-5800 affect MYCN and tumor growth?\",\"answer\":\"ATUX-1215 and ATUX-5800 reduce MYCN mRNA abundance, phosphorylation, and protein expression. PP2A activation also decreases H3K27ac at the MYCN promoter and leads to reduced tumor growth in animals, with decreased MYCN expression confirmed in tumor specimens.\"}]","PP2A activation targets MYCN in neuroblastoma | PDF",1790098625,28]